Project description:Sophocles, one of the most noted playwrights of the ancient world, wrote the tragedy Oedipus Rex in the first half of the decade 430-420 bc. A lethal plague is described in this drama. We adopted a critical approach to Oedipus Rex in analyzing the literary description of the disease, unraveling its clinical features, and defining a possible underlying cause. Our goals were to clarify whether the plague described in Oedipus Rex reflects an actual historical event; to compare it with the plague of Athens, which was described by Thucydides as occurring around the same time Sophocles wrote; and to propose a likely causative pathogen. A critical reading of Oedipus Rex and a comparison with Thucydides' history, as well as a systematic review of historical data, strongly suggests that this epidemic was an actual event, possibly caused by Brucella abortus.
Project description:Pneumonic plague (PP) is characterized by high infection rate, person-to-person transmission, and rapid progression to severe disease. In 2017, a PP epidemic occurred in 2 Madagascar urban areas, Antananarivo and Toamasina. We used epidemiologic data and Yersinia pestis genomic characterization to determine the sources of this epidemic. Human plague emerged independently from environmental reservoirs in rural endemic foci >20 times during August-November 2017. Confirmed cases from 5 emergences, including 4 PP cases, were documented in urban areas. Epidemiologic and genetic analyses of cases associated with the first emergence event to reach urban areas confirmed that transmission started in August; spread to Antananarivo, Toamasina, and other locations; and persisted in Antananarivo until at least mid-November. Two other Y. pestis lineages may have caused persistent PP transmission chains in Antananarivo. Multiple Y. pestis lineages were independently introduced to urban areas from several rural foci via travel of infected persons during the epidemic.
Project description:Microevolution associated with emergence and expansion of new epidemic clones of bacterial pathogens holds the key to epidemiologic success. To determine microevolution associated with monophasic Salmonella Typhimurium during an epidemic, we performed comparative whole-genome sequencing and phylogenomic analysis of isolates from the United Kingdom and Italy during 2005-2012. These isolates formed a single clade distinct from recent monophasic epidemic clones previously described from North America and Spain. The UK monophasic epidemic clones showed a novel genomic island encoding resistance to heavy metals and a composite transposon encoding antimicrobial drug resistance genes not present in other Salmonella Typhimurium isolates, which may have contributed to epidemiologic success. A remarkable amount of genotypic variation accumulated during clonal expansion that occurred during the epidemic, including multiple independent acquisitions of a novel prophage carrying the sopE gene and multiple deletion events affecting the phase II flagellin locus. This high level of microevolution may affect antigenicity, pathogenicity, and transmission.
Project description:The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses originating among immigrants from sub-Saharan Africa. The high rate of HIV evolution, combined with the availability of a very high density sample of viral sequences from routine clinical care has allowed the phylodynamics of the epidemic to be investigated for the first time. Sequences of the viral protease and partial reverse transcriptase coding regions from 11,071 patients infected with HIV of non-B subtypes were studied. Of these, 2774 were closely linked to at least one other sequence by nucleotide distance. Including the closest sequences from the global HIV database identified 296 individuals that were in UK-based groups of 3 or more individuals. There were a total of 8 UK-based clusters of 10 or more, comprising 143/2774 (5%) individuals, much lower than the figure of 25% obtained earlier for men who have sex with men (MSM). Sample dates were incorporated into relaxed clock phylogenetic analyses to estimate the dates of internal nodes. From the resulting time-resolved phylogenies, the internode lengths, used as estimates of maximum transmission intervals, had a median of 27 months overall, over twice as long as obtained for MSM (14 months), with only 2% of transmissions occurring in the first 6 months after infection. This phylodynamic analysis of non-B subtype HIV sequences representing over 40% of the estimated UK HIV-infected heterosexual population has revealed heterosexual HIV transmission in the UK is clustered, but on average in smaller groups and is transmitted with slower dynamics than among MSM. More effective intervention to restrict the epidemic may therefore be feasible, given effective diagnosis programmes.
Project description:BackgroundMadagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200-700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings.MethodsClinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations.Findings2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (<1%) septicaemic case, and 140 (6%) cases with unspecified clinical form. 386 (21%) of 1878 notified pneumonic plague cases were probable and 32 (2%) were confirmed. 73 (18%) of 395 notified bubonic plague cases were probable and 66 (17%) were confirmed. The case fatality ratio was higher among confirmed cases (eight [25%] of 32 cases) than probable (27 [8%] of 360 cases) or suspected pneumonic plague cases (74 [5%] of 1358 cases) and a similar trend was seen for bubonic plague cases (16 [24%] of 66 confirmed cases, four [6%] of 68 probable cases, and six [2%] of 243 suspected cases). 351 (84%) of 418 confirmed or probable pneumonic plague cases were concentrated in Antananarivo, the capital city, and Toamasina, the main seaport. All 50 isolated Yersinia pestis strains were susceptible to the tested antibiotics.InterpretationThis predominantly urban plague epidemic was characterised by a large number of notifications in two major urban areas and an unusually high proportion of pneumonic forms, with only 23% having one or more positive laboratory tests. Lessons about clinical and biological diagnosis, case definition, surveillance, and the logistical management of the response identified in this epidemic are crucial to improve the response to future plague outbreaks.FundingUS Agency for International Development, WHO, Institut Pasteur, US Department of Health and Human Services, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases, Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, AXA Research Fund, and the INCEPTION programme.
Project description:To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs. However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.
Project description:INTRODUCTION:The view that we are in the midst of a global diabetes epidemic has gained considerable ground in recent years and is often linked to the prior 'obesity epidemic'. This research explored how the diabetes epidemic was represented in United Kingdom (UK) news over the same time period that the obesity epidemic was widely reported. The research was motivated by a sociological interest in how postmodern 'epidemics' synergise with each other amidst broader political, economic, moral and sociocultural discourses. METHOD:We analysed three time-bound samples of UK news articles about diabetes: 1993 (n = 19), 2001 (n = 119) and 2013 (n = 324). Until now, UK media has had the least attention regarding portrayal of diabetes. We adopted an empathically neutral approach and used a dual method approach of inductive thematic analysis and deductive framing analysis. The two methods were triangulated to produce the findings. RESULTS:Framing of diabetes moved from medical in 1993 to behavioural in 2001, then societal in 2013. By 2001 obesity was conceptualised as causal to diabetes, rather than a risk factor. Between 2001 and 2013 portrayals of the modifiable risk factors for diabetes (i.e. diet, exercise and weight) became increasingly technical. Other risk factors like age, family history and genetics faded during 2001 and 2013, while race, ethnicity and culture were positioned as states of 'high risk' for diabetes. The notion of an 'epidemic' of diabetes 'powered up' these concerns from an individual problem to a societal threat in the context of obesity as a well-known health risk. DISCUSSION AND CONCLUSION:Portraying diabetes and the diabetes epidemic as anticipated consequences of obesity enlivens the heightened awareness to future risks in everyday life brought about during the obesity epidemic. The freeform adoption of the 'epidemic' term in contemporary health discourse appears to foster individual and societal dependence on biomedicine, giving it political, economic and divisive utility.
Project description:The molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in two intensive care units of the V. Monaldi university hospital in Naples, Italy, from May 2006 to December 2007. Genotype analysis by pulsed-field gel electrophoresis (PFGE), trilocus sequence-based typing (3LST), and multilocus sequence typing (MLST) of A. baumannii isolates from 71 patients identified two distinct genotypes, one assigned to PFGE group A, 3LST group 1, and ST2 in 14 patients and the other to PFGE group B, 3LST group 6, and ST78 in 71 patients, that we named ST2/A and ST78/B, respectively. Of these, ST2/A corresponded to European clone II identified in the same hospital during 2003 and 2004; ST78/B was a novel genotype that was isolated for the first time in May 2006 but became prevalent during 2007. The ST78/B profile was also identified in five patients from two additional hospitals in Naples during 2007. The ST2/A and ST78/B isolates were resistant to all antimicrobials tested, including carbapenems, but were susceptible to colistin. Both ST2/A and ST78/B isolates possessed a plasmid-borne carbapenem-hydrolyzing oxacillinase gene, bla(OXA-58), flanked by ISAba2 and ISAba3 elements at the 5' and 3' ends, respectively. The selection of the novel ST78/B A. baumannii clone might have been favored by the acquisition of the bla(OXA-58) gene.
Project description:BACKGROUND:The global spread of HIV-1 has been accompanied by the emergence of genetically distinct viral strains. Over the past two decades subtype C viruses, which predominate in Southern and Eastern Africa, have spread rapidly throughout parts of South America. Phylogenetic studies indicate that subtype C viruses were introduced to South America through a single founder event that occurred in Southern Brazil. However, the external route via which subtype C viruses spread to the South American continent has remained unclear. METHODOLOGY/PRINCIPAL FINDINGS:We used automated genotyping to screen 8,309 HIV-1 subtype C pol gene sequences sampled within the UK for isolates genetically linked to the subtype C epidemic in South America. Maximum likelihood and Bayesian approaches were used to explore the phylogenetic relationships between 54 sequences identified in this screen, and a set of globally sampled subtype C reference sequences. Phylogenetic trees disclosed a robustly supported relationship between sequences from Brazil, the UK and East Africa. A monophyletic cluster comprised exclusively of sequences from the UK and Brazil was identified and dated to approximately the early 1980s using a Bayesian coalescent-based method. A sub-cluster of 27 sequences isolated from homosexual men of UK origin was also identified and dated to the early 1990s. CONCLUSIONS:Phylogenetic, demographic and temporal data support the conclusion that the UK was a crucial staging post in the spread of subtype C from East Africa to South America. This unexpected finding demonstrates the role of diffuse international networks in the global spread of HIV-1 infection, and the utility of globally sampled viral sequence data in revealing these networks. Additionally, we show that subtype C viruses are spreading within the UK amongst men who have sex with men.
Project description:Klebsiella pneumoniae can lead to a wide range of diseases including pneumonia, bloodstream and urinary tract infections. During a short period of a pulmonary plague epidemic in October 2017 in Madagascar, 12 K. pneumoniae isolates were identified in ten sputum and two buboes aspirate samples. These isolates were from 12 patients suspected of plague, without epidemiological relationships, but were negative for Yersinia pestis in culture. Data were collected from the plague national surveillance system. The isolates were characterized by antimicrobial susceptibility testing and whole-genome sequencing. Real-time PCR was performed to confirm the presence of K. pneumoniae DNA in buboes. All isolates were identified as K. pneumoniae sensu stricto. Five isolates were extended-spectrum β-lactamases producers; eleven different sequence types were identified. Five isolates belonged to known hypervirulent sequence types. Our results demonstrate community-acquired pneumonia caused by K. pneumoniae isolates in patients suspected of plague stressing the importance of bed-side differential diagnosis.